Polyphenolic compounds present in the diet are bioactive molecules which elicit a wide range of response both in vivo and in vitro. The interaction of these agents with endogenous hormones can have a profound effect on target tissues and hence be important in cancer prevention. The focus of this project is to define mechanisms by which diet-derived polyphenolic agents might modulate hormone-mediated pathways. In our earlier work we examined the estrogenic/antiestrogenic effects of the isoflavones genistein, daidzein and equol in MCF-7 cells. Recently, we have demonstrated that genistein has a differential effect and increases the expression of TGF b1 mRNA in normal but not in malignant human mammary epithelial cells. Since TGF b1 is an important regulator of epithelial cell growth, our results showing that a dietary factor like genistein increases TGF b1 mRNA expression in normal human breast epithelial cells is highly significant. A number of phytochemicals that we tested inhibit the growth of tumor-derived human breast epithelial cells. This may be the result of either an increase in growth inhibitory factors like TGF b1, a suppression of growth stimulatory factors, or perhaps, both. Hence, it is important to examine the effect of dietary agents on growth stimulatory as well as inhibitory pathways. We are currently examining the effect of genistein in regulating TGF a expression in human breast cancer cells. Our studies indicate that genistein increases the expression of TGF a mRNA and protein in MCF-7 cells. In addition to these studies, the effect of dietary agents on the expression of the novel estrogen receptor b (ERb) in human mammary epithelial cells is also under investigation. These studies will assist in elucidating the various pathways modulated by dietary agents. - breast cancer, dietary factors, Estrogen, growth factors, receptors,